Pharmaceutical compositions and method for administering 3 and 4-substituted 2(5H)-furanones to a mammal for inhibiting bone loss

Abstract

3 and 4-substituted 2(5H)-furanone compounds influence the balance between bone production and bone resorption in mammals, including humans. The active compounds are administered to mammals, including humans, in an effective dose which ranges between 0.05 to 100 mg per kilogram, body weight, per day, for the purpose of influencing the balance between bone production and bone resorption, and particularly for treating osteoporosis.

What is claimed is: 
     
       1. A method for treating an imbalance between bone production and resorption in a host mammal, including a human, the method comprising the step of administering to the mammal an effective dose of a compound, or a pharmaceutically acceptable salt thereof, of the formula ##STR46## where R 1  is H or lower alkyl of 1 to 6 carbons; R is alkyl having 4 to 25 carbons, carbocyclic arylalkyl or alkenyl containing 4 to 25 carbons and one or more olephinic bonds; X is O, NH or NR 1 , where R 1  is alkyl of 1 to 20 carbons or arylalkyl;   Y is H, alkyl of 1 to 20 carbons, carbocyclic arylalkyl, carbocyclic aryl, alkenyl containing one or more olephinic bonds and 2 to 20 carbons, PO(OH) 2 , PO(OH)OR 2 , PO(OH)R 2  PO(OR 2 ) 2 , where R 2  is independently alkyl of 1 to 20 carbons or phenyl, further Y is CO--R 3 , CO--OR 3 , CONHR 3 , SO 2  R 3 , SO 2  NHR 3 , (CH 2 ) n  --O--R 3 , or (CH 2 ) n  --O--(CH 2 ) m  --O--R 3 , where n, and m, are integers and are independently 1 to 20 and R 3  is H, alkyl having 1 to 6 carbons, alkenyl containing one or more olephinic bonds and 2 to 6 carbons, carbocyclic aryl, carbocyclic arylalkyl, with the proviso that when Y is CO--R 3 , and CONHR 3  then R 3  is not hydrogen.   
     
     
       2. A method of claim 1 where the compound, or a pharmaceutically acceptable salt thereof, is administered in a daily dose of approximately 0.05 to 100 mg per kilogram of body weight of the host to be treated. 
     
     
       3. A method for treating an imbalance between bone production and resorption in a host mammal, including a human, the method comprising the step of administering to the mammal an effective dose of a compound, or a pharmaceutically acceptable salt thereof, of the formula ##STR47## where R 1  is H, alkyl of 1 to 20 carbons, alkylene having one or more double bonds, alkyne having one or more triple bonds, arylalkyl, arylalkylene having one or more double bonds, or arylalkyne having one or more triple bonds; R 2  is H, alkyl of 1 to 20 carbons, alkylene having one or more double bonds, alkyne having one or more triple bonds, arylalkyl, arylalkylene having one or more double bonds or arylalkyne having one or more triple bonds, and   R 3  is H, alkyl of 1 to 20 carbons, arylalkyl, or halogene.   
     
     
       4. A method of claim 3 where the compound, or a pharmaceutically acceptable salt thereof, is administered in a daily dose of approximately 0.05 to 100 mg per kilogram of body weight of the host to be treated. 
     
     
       5. A method for treating an imbalance between bone production and resorption in a host mammal, including a human, the method comprising the step of administering to the mammal an effective dose of a compound, or a pharmaceutically acceptable salt thereof, of the formula ##STR48## where R 1  is H, alkyl of 1 to 20 carbons, alkylene having one or more double bonds, alkyne having one or more triple bonds, arylalkyl, arylalkylene having one or more double bonds, or arylalkyne having one or more triple bonds; R 2  is H, alkyl of 1 to 20 carbons, alkylene having one or more double bonds, alkyne having one or more triple bonds, arylalkylene having one or more double bonds or arylalkyne having one or more triple bonds;   R 3  is H, alkyl of 1 to 20 carbons, arylalkyl, or halogene, and   X is H or alkyl of 1 to 20 carbons, CO--X*, CO--O--X*, CO--NH--X*, or PO(OX*,) 2  or PO(OX*,)X*, where X*, independently is H, alkyl of 1 to 20 carbons, phenyl, or substituted phenyl, with the proviso that R 1  and R 3  both are not hydrogen.   
     
     
       6. A method of claim 5 where the compound, or a pharmaceutically acceptable salt thereof, is administered in a daily dose of approximately 0.05 to 100 mg per kilogram of body weight of the host to be treated.